Epidemiology update and refractoriness to initial pharmacotherapy of chronic spontaneous urticaria: insight from an Italian primary care cohort.

Chronic spontaneous urticaria (CSU) is characterized by hives and/or angioedema for at least six weeks, impacting quality of life and healthcare costs. Objectives: This study aimed to update CSU epidemiology and assess refractoriness to initial pharmacotherapy and related determinants in Italian primary care. A cohort of patients aged 15 years and older with newly diagnosed CSU was identified from Italian primary care data from January 1, 2002, to September 30, 2022. Prevalence and incidence were calculated as % and rate per 1000 person-years, respectively. The study investigated occurrence and determinants of refractoriness to initial pharmacotherapy (H1-antihistamines and/or steroids) using multivariable Cox regression analysis. Annual CSU prevalence ranged from 0.41% in 2002 to 0.35% in 2022. The incidence was 2.07-1.93 per 1000 person-years. A cohort of 7,018 patients with CSU was identified during the study period. Of these, 50% experienced refractoriness to initial pharmacotherapy, with most events occurring within two months. Factors associated with increased refractoriness risk included age 55 years and older, autoimmune thyroiditis, asthma/COPD, unspecified allergies, and immunosuppressive drug use, including steroids. Patients who developed refractoriness were 52% more likely to be referred to dermatologists or allergists compared to non-refractory patients. These findings show that many patients, particularly those with certain coexisting conditions, do not respond well to initial CSU pharmacotherapy. By identifying these patients early through a decision support system, GPs could promptly refer them to specialists for second-line therapy evaluation.